A Phase Ib, Multi-center, Two Parallel Group, Open-label, Drug-drug Interaction Study to Assess the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 13
- 主要终点
- PK parameter AUClast for bupropion
研究概览
简要总结
This is a multi center, open-label study to evaluate the drug-drug interaction of LDE225 on the PK of bupropion and warfarin patients with advanced solid tumors. Subjects will receive 800mg daily of LDE225 and two separate doses of either bupropion or warfarin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy.
- •Protocol-defined renal , liver and bone marrow function
排除标准
- •CNS (Central Nervous System) tumors as well as history of brain metastases
- •Systemic anticancer treatment (including biologic therapy/antibodies) within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies).
- •Radiation therapy within 4 weeks before first dose
- •Investigational agents within 4 weeks before start of study therapy
- •Patients with known allergy/hypersensitivity to warfarin or bupropion and/or related compounds
- •Patients with a history of/or active bleeding disorders
- •Patients receiving treatment with vitamin K, Coumadin or other agents containing warfarin and heparin. Heparin flush to maintain patency of a central venous access device is allowed.
- •Patients receiving treatment with bupropion.
- •Patients who have neuromuscular disorders that are associated with elevated CK (Creatine phosphokinase) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- •Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C (testing is not mandatory for study entry)
- •Patients currently receiving systemic corticosteroids
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
LDE225+Warfarin
At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group.
干预措施: LDE225 (Drug)
LDE225+Warfarin
At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group.
干预措施: Wafarin (Drug)
LDE225+Bupropion
At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group
干预措施: LDE225 (Drug)
LDE225+Bupropion
At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group
干预措施: Bupropion (Drug)
结局指标
主要结局
PK parameter AUClast for bupropion
时间窗: 7 days
Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration
Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin
时间窗: 7 days
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
PK parameters Cmax for bupropion
时间窗: 7 days
Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for bupropion
时间窗: 7 days
Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration
PK parameter AUCinf for S- and R-warfarin
时间窗: 7 days
Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration
PK parameter Cmax for S- and R-warfarin
时间窗: 7 days
Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration
次要结局
- safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin(28 days cycles)
- evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors(every other cycle)
- effects of LDE225 on the pharmacodynamic activity of warfarin(7 days)
- assess the effect of LDE225 treatment on cardiac function(screening, cycle 4 and EOT)